JP5545756B2 - Novel ligands of benzo [h] quinoline species and transition metal complexes containing them and use of said complexes as catalysts - Google Patents

Description

The present invention relates to a novel tridentate ligand derived from benzo [h] quinoline and a novel transition metal complex obtained by using them, in particular, a group VIII transition metal complex selected from iron, ruthenium and osmium. About. The present invention also produces the ligands and corresponding complexes that are separated or prepared in situ by hydrogen transfer or using hydrogen gas as a catalyst for ketone, aldehyde and imine reduction reactions. Methods and the use of the complexes.

In recent years, regarding cyclometalated transition metal complexes containing tridentate (PCP, NCN, CNN) (Non-Patent Documents 1 to 3) or bidentate (PC, NC) cyclometalated ligands (Non-Patent Documents 4 and 5) Various applications have been discovered in organometallic chemistry and homogeneous catalysis. The interest in catalysis for these systems is due to the fact that they generally have a high degree of thermal stability and the fact that the presence of a metal-carbon σ covalent bond interferes with the separation of the ligand from the metal. Derived from. For example, a cyclometalated Ru complex having a bidentate CN ligand (Non-patent document 6) or a tridentate CNN ligand (Non-patent document 7) has been successfully used as a catalyst precursor in a hydrogen transfer reaction. It is used.

For bidentate N-donor ligands, in recent decades, various types of catalyst systems based on transition metals, alone or in combination with other incidental ligands such as phosphines and arenes, It should also be noted that many applications have been found in synthesis (8). Therefore, the Ru / diphosphine / diamine system having a diamine of the H ₂ N—Q—NH ₂ type is an excellent catalyst for selective homogeneous hydrogenation of various types of ketones (Non-Patent Document 9). and 10), a bidentate N-donor ligand is, [RuCl ₂ (diphosphine) (2-aminomethylpyridine)], such as, amino - if a pyridine type, these systems in 2-propanol It is particularly active as a catalyst in the reduction of carbonyl compounds by hydrogen transfer (Non-patent Document 11 and Patent Document 1). The catalytic activity in hydrogen transfer is to use a ligand such as 6-aryl-2- (aminomethyl) pyridine, which bonds the group capable of providing a cyclometallation reaction to the 2-aminomethylpyridine skeleton. (Non-patent Document 12).

Reduction of carbonyl compounds such as ketones and aldehydes is a reaction that has gained widespread practical interest and has led to intensive research activities in recent years. In this regard, two other different hydrogenation methods have been developed, as well as methods based on biocatalytic reduction methods and the use of metal hydrides such as LiAlH ₄ :
1) Reduction with molecular hydrogen using a catalyst system based on transition metals;
2) Catalytic reduction by hydrogen transfer using formic acid or 2-propanol as hydrogen donor.

Good results have been obtained with both methods, particularly in systems based on ruthenium (II) complexes containing various ligand types. From an industrial point of view, both technologies offer advantages and losses. In this respect, the carbonyl compound hydrogenation reaction using hydrogen gas is generally carried out under pressure. Although the reaction has the advantage of having a very active catalyst system operating at moderate temperatures, it can be a source of danger and requires a dedicated plant. In processes based on transition reactions, 2-propanol is usually used as both a hydrogen source and reaction solvent, and offers the advantages of low boiling point, low toxicity and low environmental impact. Due to the simplicity of operation and the good results it can give, catalytic hydrogen transfer is a useful alternative to reduction with hydrogen primarily for small and medium scale reactions. However, it should be noted that the catalyst systems available for hydrogen transfer are generally less active. This causes long reaction times and reduced plant availability, in addition to the risk of catalyst deactivation and decomposition over time.

For rare exceptions, it is also noted that the catalytic activity in hydrogen transfer is less active in hydrogenation and vice versa (Non-Patent Documents 13 and 14).

Hydrogenation reaction For reduction using molecular hydrogen, catalyst systems based on various transition metals (Ir, Rh, Pd, Ni) are used, and in particular, ruthenium derivatives are attracting attention. [RuCl ₂ (phosphine) ₂ (1,2-diamine)] and [RuCl ₂ (diphosphine) (1,2-diamine)] type compounds in the basic medium are homogeneous phases of various types of ketones. Is an excellent catalyst for selective hydrogenation. Furthermore, with the appropriate combination of chiral diphosphines and diamines, enantioselective hydrogenation of carbonyl compounds can be achieved by formation of optically active alcohols with high enantiomeric excess. The reaction is generally performed using hydrogen under pressure and moderate temperature (Non-patent Documents 15 to 19). [RuCl 2 _{(diphosphine)} (2-aminomethylpyridine)] amine, such as - complexes containing pyridine type bidentate ligands, depending on the diphosphines and solvent, in both hydrogenation and hydrogen transfer reaction It should be noted that it can exhibit catalysis (Non-Patent Documents 20 and 21). A series of ruthenium compounds with a ruthenium complex containing tetradentate diamino-diphosphine and diimino-diphosphine ligands as well as Ru / diphosphine / diamine systems and phosphino-oxazoline type ligands Interesting results have also been obtained with catalytic hydrogenation using (Non-Patent Documents 23 and 24).

Hydrogen transfer In the transfer reduction of a carbonyl compound, 2-propanol or a formic acid / triethylamine mixture which is also a reaction solvent is usually used as a hydrogen source (Non-patent Documents 25 to 30).

Although catalysts based on transition metals such as rhodium and iridium were used (Non-Patent Documents 31-33 and Patent Documents 3 and 4), ruthenium derivatives were used to achieve the most interesting results for enantioselective reduction of ketones. These are in particular arene-ruthenium complexes with diamine or β-aminoalcohol ligands (Non-Patent Documents 34 to 36 and Patent Document 5), diphosphine-diamine and diphosphine-diimine type tetradentate ligands (non- Patent Document 37), complexes having an oxazoline ligand (Non-Patent Document 38 and Patent Document 6) and complexes having an oxazoline ferrocenylphosphine ligand (Non-Patent Document 39). In addition, using 2-aminomethylpyridine ligand, the TOF number (turnover frequency) = 50% conversion per mole of catalyst per hour is possible to reach 10 ⁵ h ⁻¹ . A highly catalytic complex of [RuCl ₂ (P ₂ ) (2-aminomethylpyridine)] (monodentate or bidentate phosphine P-phosphorus atom) having a molar number of ketones converted to alcohol was obtained. (Non-Patent Document 40 and Patent Document 1). A tridentate ligand such as 6-aryl-2- (aminomethyl) pyridine containing an aryl group capable of providing cyclometalation (TOF to 10 ⁶ h ⁻¹ ) is potentially used. Thus, the catalytic activity further increases (Non-patent Documents 41 and 42).

Formula RuX [C ₆ H ₃ (CH ₂ PPh ₂ ) ₂ -2,6] (PPh) with a stable Ru-C aryl linkage, described by van Koten and colleagues (Non-Patent Documents 43 and 44). ₃ ) Published by Mathieu containing a highly active catalyst system for the non-enantioselective reduction of “sandwich-aryl” type ketones of (X═Cl, CF ₃ SO ₃ ) and a tridentate pyridine ligand (Non-Patent Documents 45 and 46) show TOF values of up to 90000 h ⁻¹ for acetophenone reduction, even though their rapid deactivation limits their use in organic synthesis. It should be stated.

Furthermore, in a recent study, Mathey and Le Floch (47) include the ligand N, P bidentate 1- (2-methylpyridine) -2,5 diphenyl phosphor. A new arene-ruthenium catalyst has been described. This shows a TOF number of up to 10 ⁶ h ⁻¹ for many ketones. However, a very long time (several days at 90 ° C.) is required, limiting its practical use.

In order to keep the economic advantage of the reduction of ketones to alcohols by hydrogen transfer, the synthesis of new catalysts with high activity and productivity is a fundamental target. This is particularly important when the catalyst system can lead to enantioselective reduction as it provides optically active alcohols from prochiral ketones.

International Publication No. 2005/1058191 Pamphlet US Pat. No. 6,878,852 US Pat. No. 6,372,93 US Pat. No. 6,545,188 US Pat. No. 6,184,381 US Pat. No. 6,451,727

M. Albrecht, G. van Koten, Angew. Chem. Int. Ed. 2001, 40, 3750 M. E. van der Boom, D. Milstein, Chem. Rev. 2003, 103, 1759 J. T. Singleton, Tetrahedron 2003, 59, 1837 W. Baratta, P. Da Ros, A. Del Zotto, A. Sechi, E. Zangrando, P. Rigo Angew. Chem. Int. Ed., 2004, 43, 3584 J.B.Sortais, V. Ritleng, A. Voelklin ,, A. Holuigue, H. Smail, L. Baryol, C. Sirlin, G.K.M.Verzijl, A.H.M.de Vries, M. Pfeffer, Org. Lett, 2005,7, 1247 J.B.Sortais, L. Baryol, C. Sirlin, A.H.M.de Vries, J. G. de Vries, M. Pfeffer, Pure Appl. Chem, 2006, 78, 475 W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Zanette, E. Zangrando, P. Rigo, Angew. Chem. Int. Ed. 2005, 44, 6214 M. Lemaire et al. Chem. Rev., 2000, 100, 2159 R. Noyori, T. Ohkuma, Angew. Chem., Int. Ed. Engl. 2001, 40, 40 R.H. Morris et al. Coord. Chem. Rev. 2004, 248, 2201 W. Baratta, E. Herdtweck, K. Siega, M. Toniutti, P. Rigo, Organometallics 2005, 24, 1660 W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Zanette, E. Zangrando, P. Rigo, Angew. Chem. Int. Ed. 2005, 44, 6214 T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K. MuCiz, R. Noyori, J. Am. Chem. Soc. 2005, 127, 8288 F. Naud, C. Malan, F. Spindler, C. Ruggerberg, A. T. Schimdt, H-U Blaser, Adv. Synth. Catal. 2006, 348, 47 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Ed. R. Noyori, 1994, pp. 56-82 T. Ohkuma, H. Ooka, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995, 117, 10417 R. Noyori, T. Ohkuma, Angew. Chem., Int. Ed. Engl. 2001, 40, 40 K. V. L. Crepy, T. Imamoto, Adv. Synth. Catal. 2003, 345, 79 R.H. Morris et al. Coord. Chem. Rev. 2004, 248, 2201 W. Baratta, E. Herdtweck, K. Siega, M. Toniutti, P. Rigo, Organometallics 2005, 24, 1660 T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K. MuCiz, R. Noyori, J. Am. Chem. Soc. 2005, 127, 8288 R.H.Morris et al. Chem. Eur. J. 2003, 9, 4954 H.A.McManus, P.J.Guiry, Chem. Rev. 2004, 104, 4151 T. Naud et al., Adv. Synth. Catal. 2006, 348, 47 G. Zassinovich, G. Mestroni, S. Gladiali, Chem. Rev. 1992, 92, 1051 R. Noyori, S. Hashiguchi, Acc. Chem. Res. 1997, 30, 97 J.-E.Backvall, J. Organomet. Chem. 2002, 652, 105 M.J.Palmer, M. Wills, Thetrahedron: Asymmetry 1999, 10, 2045 J. S. M. Samec, J. E. Backvall, P. G. Andersson, P. Brandt, Chem. Soc. Rev. 2006, 35, 237 S. Gladiali, E. Alberico, Chem. Soc. Rev. 2006, 35, 226 M.J.Palmer, M. Wills, Thetrahedron: Asymmetry 1999, 10, 2045 A.C.Hillier, H.M.Lee, E.D.Stevens, S.P, Nolan, Organometallics 2001, 20, 4246 J Backvall, J. Organomet. Chem. 2002, 652, 105 K.-J.Haack, S. Hashiguchi, A. Fujii, T. Ikariya, R. Noyori, Angew. Chem. Int. Ed. Engl. 1997, 36, 285 K. Everaere, A. Mortreaux, J. Carpentier, Adv. Synth. Catal. 2003, 345, 67 T. Ikariya, K. Murata, R. Noyori, Org. Biomol. Chem. 2006, 4, 393 J.-X.Gao, T. Ikarya, R. Noyori, Organometallics, 1996, 15, 1087 Y. Jiang, Q. Jiang, X, Zhang, J. Am. Chem. Soc. 1998, 120, 3817 Y. Nishibayashi, I. Takei, S. Uemura, M. Hidai, Organometallics 1999, 18, 2291 W. Baratta, E. Herdtweck, K. Siega, M. Toniutti, P. Rigo, Organometallics 2005, 24, 1660 W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Zanette, E. Zangrando, P. Rigo, Angew. Chem. Int. Ed. 2005, 44, 6214 W. Baratta, M. Bosco, G. Chelucci, A. Del Zotto, K. Siega, M. Toniutti, E. Zangrando, P. Rigo, Organometallics 2006, 25, 4611 P. Dani, T. Karlen, R. A. Gossage, S. Gladiali, G. van Koten, Angew. Chem., Int. Ed. Engl. 2000, 39, 743 M. Gagliardo, P.A.Chase, S. Brouwer, G.P.M.van Klink, G. van Koten Organometallics, 2007, 26, 2219 H. Yang, M. Alvarez, N. Lugan, R. Mathieu, J. Chem. Soc., Chem. Commun. 1995, 1721 H. Yang, M. Alvarez-Gressier, N. Lugan, R. Mathieu, Organometallics 1997, 16, 1401 C. Thoumazet, M. Melaimi, L. Ricard, F. Mathey, P. Le Floch, Organometallics 2003, 22, 2580

Accordingly, one object of the present invention is to identify novel HCNN type ligands to be used in catalysis and novel complexes of Group VIII metals obtained using the ligands. is there. Another object of the present invention is a cyclometallated CNN ligand, which can be used as a highly active catalyst in asymmetric and asymmetric reduction of carbonyl or imino compounds using hydrogen gas or by hydrogen transfer, Synthesis of Group VIII transition metal complexes consisting of iron, ruthenium and osmium, including those that are chiral and phosphine after all. Another object of the present invention can be used as a catalyst generated in situ during asymmetric and asymmetric reduction of carbonyl or imino compounds using hydrogen gas or by hydrogen transfer to alcohol. It is to obtain ruthenium (II) and osmium (II) complexes.

In order to achieve the above object, the inventors have the formula (I)



(In the formula, R ₁ is a cycloaliphatic aliphatic group or an aromatic group;
R _{2, R 3} and _{R 4} is equal to each other or different, and a hydrogen atom, an aliphatic group or an aromatic group, a halogen atom, alkoxo (Alkoxo) group, a nitro group, a cyano group)
A new species of compound derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group at the 2 position, identified by is identified.

The ligands of the invention are represented by formula (Ia) (HCNN) and when the deprotonated form is represented by formula (Ib) (CNN):

A family of ligands for the synthesis of transition metal complexes to be used as catalysts in organic synthesis reactions.

The ligand of the present invention having a transition metal is selected from Group VIII consisting of iron, ruthenium and osmium, and is coordinated to the metal via the nitrogen atom of the pyridine ring and the nitrogen atom of the primary amine group Have the ability to act as a tridentate ligand. In particular, said ligand having a Group VIII transition metal selected from iron, ruthenium and osmium results in a cyclometalation reaction at position 14, forming a metal-carbon σ bond and two five-membered rings, General formula (II)

Represented by the following structural formula

(Where:
M = Group VIII transition metal selected from iron, ruthenium and osmium;
X = halogen, hydrogen, alkoxide (OR);
P = phosphorus atom of monodentate or bidentate phosphine (L), or optically active diphosphine (L);
And R ₁ , R ₂ , R ₃ and R ₄ may have the above meanings, which are residues of the novel CNN ligand of formula (Ib))
To form a complex corresponding to

For the reduction of ketones and aldehydes to alcohols and further to the reduction of imines to amines, the preferred transition metals are ruthenium and osmium. Thus, the inventors have found that in the presence of a base, in a novel species of ruthenium (II) and osmium (II) complexes with CNN-type ligands in combination with recovery solutions, monodentate or bidentate phosphines. Used for the reduction of carbonyl compounds in both hydrogen transfer reactions in 2-propanol and hydrogenation reactions with molecular hydrogen, which may also achieve enantioselective synthesis by appropriate combination with chiral phosphines A catalyst with very high catalytic activity was identified.

It should be noted that few examples of the use of osmium derivatives as catalysts in the reduction reaction of carbonyl compounds have been reported. Because they are probably more expensive and generally less active than the corresponding ruthenium derivatives (RH Morris in The Handbook of Homogeneous Hydrogenation, 2007, 1, 45 -Eds. JG de Vries, CJ Elsevier- Wiley -VCH, Weinheim). Compared to ruthenium, the use of a more stable osmium derivative has the advantage that reduction at higher temperatures can be carried out.

Accordingly, the present invention provides compounds of formula (Ia) and (Ib)

(Where:
R ₁ is a cycloaliphatic aliphatic group or an aromatic group;
R _{2, R 3} and _{R 4} is equal to each other or different, and a hydrogen atom, an aliphatic group or an aromatic group, a halogen atom, alkoxo (Alkoxo) group, a nitro group, a cyano group)
HCNN / CNN type ligands represented by

The present invention also provides a compound of the general formula (II)

Wherein M, X, L and L ′ can be as follows:
A Group VIII transition metal selected from M, iron, ruthenium and osmium;
X, halogen, hydrogen, alkoxide (OR in which R can be an aliphatic group or an aromatic group);
L, a ligand selected from the group consisting of :
^{a) R} 1, R ² and ^{R 3} are equal or differ from each other, and, an aliphatic group or an aromatic group, a monodentate phosphine of general formula ^PR 1 ^R 2 ^{R 3;}
b) Z is a hydrocarbon chain x is 2, 3 or 4 equal _{PR '2 (CH 2) x} PR'' is optionally substituted with priority type ₂ diphosphine, R' and R '' It becomes equal or different, and, an aliphatic group or an aromatic _{group, PR '2 -Z-PR'} '2 type bidentate phosphine;
c) an optically active diphosphine;
And when ligand L is selected from group b) or c), m is equal to 1, and when ligand L is selected from group a), m is equal to 2, and in this case , the ligand L is equal or different, equal m is 1 or 2 with the proviso that;
L ′, formula (Ib)



(Wherein, _{R 1} is H or an aliphatic group or an aromatic group, _and, R 2, _{R 3} and _{R 4} are equal or differ from each other, and a hydrogen atom, an aliphatic group and an aromatic group, halogen atom, alkoxo group, a nitro group, a cyano group)
CNN type tridentate cyclometalated ligand)
It is related with the transition metal complex shown by these.

Another aspect of the present invention is a process for producing a transition metal complex, also obtained in situ, and reduction of said ketone or aldehyde from alcohol to ketone or aldehyde, using molecular hydrogen or by hydrogen transfer In the reaction, it is a transition metal complex obtained directly in situ by the above method.

Another aspect of the present invention is the use of the transition metal complex as a catalyst for the reduction reaction of carbonyl or imino compounds using hydrogen gas or by hydrogen transfer.

These and other aspects, as well as features and advantages of the present invention will become more apparent from the following detailed description, given by way of non-limiting illustration of the invention itself, and by the preferred embodiments. .

For the purposes of the present invention, we have a benzo [h] quinoline derivative having a —CHR ₁ —NH ₂ group in the second position represented by general formula (Ia), and benzyl carbon therein, Has found that the ligand is a chiral center suitable for the synthesis of transition metal complexes used as catalysts in hydrogen transfer or hydrogen gas reduction reactions of carbonyl compounds. Due to their electronic and steric properties, these ligands are potentially tridentate, which can coordinate to the metal via quinolinate nitrogen (sp2) and primary amine nitrogen (sp3); And the cyclometallation reaction also leads to the formation of a metal-carbon σ bond and two five-membered rings.

As a result of research, it was discovered that various transition metal complexes can be obtained efficiently. In the complex, a ligand derived from benzo [h] quinoline in the presence of an accompanying phosphine-type ligand functions as a cyclometalated tridentate that forms a stable complex, and the base In the presence, it has an interesting use as a catalyst in the reduction reaction of carbonyl or imino compounds.

Accordingly, the present invention provides a Group VIII transition metal consisting of iron, ruthenium or osmium in combination with a monodentate or bidentate phosphine at the 14th position via a metal-carbon σ bond and via two nitrogen atoms. A novel benzo [h] quinoline derivative (HCNN, Ia) having a —CHR ₁ —NH ₂ group at the second position, which can function as a cyclometalated tridentate ligand (CNN, Ib) Regarding species.

In particular, the present invention provides CNN-type ligands and phosphines as efficient catalysts in the catalytic reduction reaction of ketones and aldehydes to alcohols by either hydrogen transfer or hydrogen gas in the presence of a strong base. Including novel transition metal complex species of Group VIII transition metals selected from iron, ruthenium and osmium, and their use. If the phosphine and / or benzo [h] quinoline type ligand used is optically active, various types of optically active alcohols can be generated starting from carbonyl compounds such as prochiral ketones.

As previously stated, the ligands of the present invention are a family of benzo [h] quinoline derivatives (HCNN) having a —CHR ₁ —NH ₂ group in the 2 position,

As shown by the general formula (Ia), the benzylic carbon may optionally be a chiral center and R ₁ may be H, or an aliphatic or aromatic group, and R 1 ₂ , R ₃ and R ₄ can be equal or different, and can be a hydrogen atom, an aliphatic group and an aromatic group, a halogen atom, an alkoxo group, a nitro group, a cyano group.

The benzo [h] quinoline family (Ia; HCNN), either by reduction of the corresponding 2-cyano derivative (R1 = H) or reduction of the appropriate 2-ketoxime (R1 = aliphatic or aromatic) Various types of ligands can be produced.

In the presence of a monodentate or bidentate phosphine and a base such as triethylamine, the HCNN ligand (Ia) reacts with a suitable precursor of a transition metal selected from iron, ruthenium and osmium, preferably ruthenium and osmium. Give complexes that function as tridentate cyclometalated CNN (Ib) ligands that coordinate to the metal via quinoline nitrogen (sp ² ) and primary amine nitrogen (sp ³ ), P = monodentate Or the following structural formula having a phosphorus atom of a bidentate phosphine

Two 5-membered rings with a metal-carbon σ bond are formed at the 14th position.

The synthesis of three different HCNN-type ligands (Ia) is given below via a non-limiting example.

The coordination characteristics of these three ligands are very similar to each other, all easily lead to cyclometallation reactions using Ru (II) and Os (II), and monoanionic tridentate Acts as a ligand.

For the preparation of the complexes, those metal precursors comprising monodentate phosphines of the formula MX ₂ P _n (M = Ru, Os; X = Cl, Br; P = PPh ₃ ; n = 3, 4) are preferably used. .

In general, the process for the preparation of the complex involves the metal precursor, phosphine ligand and HCNN coordination in an inert solvent, preferably toluene, in the presence of triethylamine which promotes the cyclic methanation reaction. It consists of a reaction between the children.

Thus, the complex of the present invention can be a complex of ruthenium (II) and osmium (II), having the general formulas (III) and (IV)

(Where:
X, L, L ′ may have the previously mentioned meanings)
Have

The CNN-type ligands of the present invention are novel and in combination with monodentate or bidentate phosphines, and group VIII transition metals, preferably ruthenium (II) and osmium (II), with 2-propanol as the hydrogen donor. The complex used is a particularly active catalyst in reduced carbonyl compounds such as ketones used, with hydrogen gas in alcohol or by hydrogen transfer.

For the purposes of the present invention, from combinations of different meanings of X, L, L ′ and m, and when the transition metal is ruthenium, a ruthenium (II) complex of the general formula given below is obtained:
A ruthenium (II) complex of the formula (V)

(Where:
X is halogen, hydrogen, alkoxide (OR);
L is an equal or different monodentate phosphine selected from group a);
L ′ is a CNN type tridentate ligand of formula (Ib));
A ruthenium (II) complex represented by the formula (VI)

(Where:
X is halogen, hydrogen, alkoxide (OR);
L is a bidentate phosphine selected from b) group or c) an optically active diphosphine selected from group;
L ′ is a CNN type tridentate ligand of the formula (Ib))

For the purposes of the present invention, the preferred ligand X is chloride or bromide, the preferred ligand L in group a) is PPh ₃ ; and the preferred ligand L in group b) is PPh ₂ (CH ₂ ). ₄ PPh ₂ ; c) Preferred ligands L in the group include:

On the other hand, a preferred meaning of R ₁ , R ₂ , R ₃ and R ₄ of the L ′ ligand of formula (Ib) is H (CNN—H).

When the transition metal is osmium and m is equal to 2, the osmium (II) complex according to the general formula (VII):

(Where
X is halogen, hydrogen, alkoxide (OR);
L is an equal or different monodentate phosphine selected from group a);
L ′ is a CNN type tridentate ligand of the formula (Ib))
Is obtained.

When the transition metal is osmium and m is equal to 1, the complex is of formula (VIII)

(Where
X is halogen, hydrogen, alkoxide (OR);
L is a bidentate phosphine selected from b) group or c) an optically active diphosphine selected from group;
L ′ is a CNN type tridentate ligand of the formula (Ib))
By

For the purposes of the present invention,
A preferred ligand X is chloride or bromide;
Preferred ligands L of -b) group is an _{PPh 2 (CH 2) 4 PPh} 2;
Preferred ligands L of the group -c) are (R, S) -JOSIPHOS, (S, R) -JOSIPHOS ^* , (S, S) -SKEWPHOS, (S) -MeO-BIPHEP;
On the other hand, a preferred meaning of R ₁ , R ₂ , R ₃ and R ₄ of the ligand L ′ of formula (Ib) is H (CNN—H).

Specific examples of complexes that have been isolated and used in catalysis are listed below, referring to non-limiting examples of the present invention.

1. General formula (V)

Wherein L ′ is a CNN—H ligand, L is PPh ₃ and X═Cl (6),

Is)
Ruthenium complex.

2. Formula (VI)

Wherein L ′ is a CNN—H ligand and X═Cl, H, OR and L are diphosphine PPh ₂ (CH ₂ ) ₄ PPh ₂

X = Cl (7); X = H (8); X = O—CH (p—C ₆ H ₄ F) ₂ (9)
Wherein, L '= CNN-Me ( 10), CNN-Bu t (11); X = Cl

^{_{R 1 = Me (10),}} Bu t (11)
Where L ′ is a CNN—H ligand and L is a chiral diphosphine shown as follows:

Ruthenium complex.

RuCl the ^{P-P *} represents a chiral diphosphine ^[P-P *] The method of synthesis (CNN-H) type complex, as indicated by ³¹ P NMR spectra of the separated product, different diastereomers Leading to the formation of a mixture of (disasteromers). The resulting diastereomeric mixture was used as such in the catalysis test.

3. Osmium (II) complex of formula (VIII)

Wherein L ′ is a CNN—H ligand, L is diphosphine PPh ₂ (CH ₂ ) ₄ PPh ₂ and X═Cl (7a); X═H (8a); X═O— _{CH (p-C 6 H 4} F) 2 is a (9a))

A. Ligand synthesis The synthetic route used for HCNN ligands in an embodiment where R ₁ = R ₂ = R ₃ = R ₄ = H is schematically shown in Scheme 1.

It expresses by.

2-Cyanobenzo [h] quinoline is prepared by the method published by Chelucci et al. (Tetrahedron: Asymmetry 1999, 10, 543) using hydrogen gas in acetic acid with 10% Pd on carbon. Reduced.

The ligand with R ₁ = Me, CMe ₃ in racemic form was prepared from 2-chlorobenzo [h] quinoline prepared by the method of Capelli et al. (J. Med. Chem. 1998, 41, 728). Prepared by the method summarized in the following scheme (Scheme 2) originating from the resulting 2-bromobenzo [h] quinoline.

These syntheses are given in Examples 1-3.

B. Synthesis of <br/> complexes of the present invention the ruthenium complex (6-15) includes compounds _{RuCl 2 (PPh 3) 3 (} 4) as starting product.

The compounds are commercially available or can be prepared by reaction of RuCl ₃ hydrate and triphenylphosphine (R. Holm, Inorg. Synth. 1970, 12, 238). On the other hand, the complex RuCl ₂ [PPh ₂ (CH ₂ ) ₄ PPh ₂ ] (PPh ₃ ) (5)

Was prepared according to procedures published in the literature (CW Jung, PE Garrou, PR Hoffman, KG Caulton, Inorg. Chem. 1984, 23, 726).

Complex (6) was obtained by reacting HCNN-H (1) and RuCl ₂ (PPh ₃ ) ₃ (4) in toluene under reflux in the presence of triethylamine. Subsequent to the procedure of (6), HCNN-H (1) and (5) were reacted to obtain derivative (7). On the other hand, complexes (10) and (11) were produced using HCNN-Me (2) and HCCN-tBu (3). Catalysts (12-15) were prepared by reacting complex (4) with chiral phosphine in toluene under reflux followed by addition of HCNN-H ligand (1) in the presence of triethylamine. Derivatives (8) and (9) were prepared from (7) by reaction with sodium isopropoxide and in the case of (9) adding 4,4′-difluorobenzophenone.

All operations were performed under an inert gas atmosphere and the solvent used was dried and distilled before use. The synthesis is given in Examples 4-13.

C. Synthesis of complexes of synthetic <br/> invention osmium complex (7a) includes a triphenyl phosphine _{[(NH 4) 2 OsCl 6} ] may be prepared by reacting a compound OsCl ₂ as the starting product ( PPh ₃ ) ₃ (4a) is included (Elliott, GP; McAuley, NM; Roper, WR Inorg. Synth. 1989, 26, 1849).

On the other hand, phosphine PPh ₂ (CH ₂ ) ₄ PPh ₂ and OsCl ₂ (PPh ₃ ) ₃ are reacted in methylene chloride, and the product thus obtained is subsequently reacted in toluene under reflux and triethylamine in some situations, by treatment with HCNN-H (1), to produce a complex _{OsCl 2 (CNN-H) [} PPh 2 (CH 2) 4 PPh 2] (7a).

Derivatives (8a) and (9a) were prepared from (7a) by reaction with sodium isopropoxide and, in the case of (9a), 4,4'-difluorobenzophenone.

The synthesis is given in Examples 14-16.

The synthesis and properties of ruthenium (II) complexes (6-15) and osmium (II) complexes (7a-9a) are given in detail below. All syntheses were carried out under an argon atmosphere and using distilled or previously degassed solvents.

Ligand and complex were characterized by elemental analysis and ¹ H NMR, ¹³ C { ¹ H} NMR and ³¹ P { ¹ H} NMR nuclear magnetic resonance measurements. All complexes with CNN-R ligands have a characteristic signal for carbon bound to the metal at δ = 177-183 ppm when the metal is ruthenium and δ = 157 ppm when the metal is osmium. Indicated.

Example 1: Preparation of HCNN-H ligand A compound from 2-cyanobenzo [h] quinoline prepared by the method given in Shelkki, G (Chelucci, G) et al., Tetrahedron: Asymmetry 1999, 10, 543: Got.

1- (Benzo [h] quinolin-2-yl) methanamine. A mixture of 2-cyanobenzo [h] quinoline (2.04 g, 10.0 mmol) and 10% palladium on carbon (0.40 g) in acetic acid (120 ml) was converted into a per reactor (2 reactors) using hydrogen gas at a pressure of 2 atm. Hydrogenated at ambient temperature in a Parr reactor). After 4 hours, when the time absorbance of 2 hydrogen equivalents was observed, the reaction mixture was filtered and the solvent was evaporated under reduced pressure. The oily residue was dissolved with ethyl ether and the mixture was washed with 10% NaOH solution until an alkaline pH was achieved. The organic phase was then separated and dried over Na ₂ SO ₄ . The solvent was evaporated and the residue was purified by flash chromatography using MeOH as eluent. 1.87 g (90% yield) of 1- (benzo [h] quinolin-2-yl) methanamine was obtained in the form of a red solid.
Elemental analysis calculated for C ₁₄ H ₁₂ N ₂ : C, 80.74; H, 5.81; N, 13.45. Detection: C, 80.55; H, 5.91; N, 13.66. ¹ H NMR (CDCl ₃ ): δ 9.58 (d, J = 7.4 Hz, 1H; aromatic proton), 8.11- 7.71 (m, 7H; aromatic proton), 4.37 (s, 2H; CH ₂ ), 2.90 (s, 2H; NH ₂ ¹³ C { ¹ H} NMR (CDCl ₃ ): δ 158.5 (s, NCCH ₂ ; aromatic proton), 143.9 (s, NCC; aromatic carbon), 134.4-118.2 (m; aromatic carbon), 46.3 (s; CH ₂ )

The starting products for the synthesis of two HCNN-R ligands (R = Me, ^t Bu) (Examples 1 and 2) are described in Cappeli, A et al., J. Med. Chem. 1998, 41, 2-Bromobenzo [h] quinoline obtained from 2-chlorobenzo [h] quinoline prepared by the method given by 728.

Example 2 Preparation of HCNN-Me Ligand (Benzo [h] quinolin-2-yl, prepared by reacting NH ₂ OH · HCl with 1- (benzo [h] quinolin-2-yl) ethanone ) Ligand was obtained by reduction of methyl ketoxime with Zn.

2 Bromobenzo [h] quinoline. A mixture of 2-chlorobenzo [h] quinoline (2.43 g, 11.4 mmol), bromotrimethylsilane (3.00 ml, 22.7 mmol) and propionitrile (12 ml) was heated under reflux for 111 hours. The reaction mixture was then poured into a 10% NaOH solution containing ice. The organic phase was separated and the aqueous phase was extracted with Et ₂ O (3 × 15 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated under reduced pressure. Chromatography (SiO _2, petroleum ether / acetic acid (acetate) = 9/1) the residue to give the 2-bromobenzo [h] quinoline in the form of a yellow solid: 2.82 g (96% yield) of Melting point: 113-114 ° C.
Elemental analysis calculated for C ₁₃ H ₈ BrN (%): C, 60.49; H, 3.12; N, 5.43. Detection: C, 60.33; H, 3.25; N, 5.38. ¹ H NMR (CDCl ₃ ) : δ 9.35-9.15 (m, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.92-7.84 (m, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.74-7.67 (m, 2H), 7.61 (dd, J = 8.4 Hz, J = 1.5 Hz, 2H). ¹³ C { ¹ H} NMR (CDCl ₃ ): δ 147.1, 140.7, 138.0, 133.7, 130.4, 128.7, 128.2, 127.7, 127.3 , 126.1, 125.1, 124.7, 124.5.

1- (Benzo [h] quinolin-2-yl) ethanone. A solution of 2-bromobenzo [h] quinoline (1.52 g, 5.89 mmol) in THF (36 ml) was cooled to −78 ° C. After 10 minutes, a solution of 2.5M n-butyllithium in n-hexane (2.47 ml, 6.18 mmol) was added. The resulting dark red solution was stirred again at −78 ° C. for 1 hour, after which N, N-dimethylacetamide (0.60 ml, 6.45 mmol) was added dropwise. The solution was stirred at −78 ° C. for 1 hour and slowly warmed to ambient temperature. A solution of 1M HCl (7.4 ml, 7.4 mmol) was then added, the organic phase was separated and the aqueous phase was extracted with Et ₂ O (2 × 15 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated under reduced pressure. The residue is purified by flash chromatography (petroleum ether / acetic acid = 95/5) and 1.00 g (77% yield) of 1- (benzo [h] quinolin-2-yl) ethanone in the form of a yellow solid. Obtained: mp 113-115 ° C.
Elemental analysis calculated for C ₁₅ H ₁₁ NO (%): C, 81.43; H, 5.01; N, 6.33. Detection: C, 81.43; H, 5.01; N, 6.33. ¹ H NMR (CDCl ₃ ): δ 9.08 (dd, J = 8.1 Hz, J = 1.5 Hz, 1H), 8.02 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.80-7.70 (m, 1H), 7.69-7.55 (m, 3H), 7.39 (d, J = 9 Hz, 1H), 2.83 (s, 3H). ¹³ C { ¹ H} NMR (CDCl ₃ ): δ 200.2, 151.0, 144.8, 135.9, 133.3 , 131.1, 129.5, 128.2, 127.8, 127.6, 127.1, 124.5, 124.1, 118.3, 25.4.

1- (Benzo [h] quinolin-2-yl) ethanone oxime. 1- (Benzo [h] quinolin-2-yl) ethanone (2.62 g, 11.84 mmol) and hydroxylamine hydrochloride (1.52 g, 21 in 96% ethanol (100 ml) for 30 hours at ambient temperature. .87 mmol) solution was stirred. The reaction was monitored by TLC (SiO ₂ , petroleum ether / acetic acid = 9/1). Most of the solvent was then evaporated under reduced pressure and the residue was dissolved with CH ₂ Cl ₂ and saturated NaHCO ₃ solution. The resulting mixture was stirred vigorously for 30 minutes, then the organic phase was separated and the aqueous phase was extracted with CH ₂ Cl ₂ (2 × 20 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated to give 2.70 g (97% yield) of the oxime of 1- (benzo [h] quinolin-2-yl) ethanone in the form of a yellow solid. And used in the next step without further purification: mp 200-202 ° C.
Elemental analysis calculated for C ₁₅ H ₁₂ N ₂ O (%): C, 76.25; H, 5.12; N, 11.86. Detection: C, 76.44; H, 5.15; N, 11.89.

1- (Benzo [h] quinolin-2-yl) ethanamine. In a mixture consisting of 30% NH ₃ / H ₂ O / 96% EtOH (39.5 / 26.3 / 26.3 ml), the oxime of 1- (benzo [h] quinolin-2-yl) ethanone (2.60 g 11.0 mmol) and ammonium acetate (1.05 g, 13.6 mmol) were stirred for 30 minutes at ambient temperature. Then, over a period of 2 hours (at ambient temperature), zinc in powder form (3.95 g, 60.4 mmol) was added and the resulting mixture was heated at reflux for 3 hours. The gray precipitate that formed was filtered under reduced pressure, the solvent was evaporated and the residue was alkalized with 10% NaOH and extracted with Et ₂ O (3 × 30 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography using MeOH as eluent and 1.88 g (77% yield) of 1- (benzo [h] quinolin-2-yl) ethanamine in the form of an orange oil. Obtained.
Elemental analysis calculated for C ₁₅ H ₁₄ N ₂ (%): C, 81.05; H, 6.35; N, 12.60. Detection: C, 81.24; H, 6.38; N, 12.58. ¹ H NMR (CDCl ₃ ): δ 9.36 (d, J = 8.1 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.80-7.59 (m, 4H), 7.47 (d, J = 8.1 Hz, 1H), 4.37 (q, J = 6.6 Hz, 1H), 2.26 (s, 2H), 1.56 (d, J = 6.6 Hz, 3H). ¹³ C { ¹ H} NMR (CDCl ₃ ) : δ 164.2, 145.5, 136.3, 133.6, 131.3, 127.9, 127.7 127.0, 126.7, 125.1, 124.9, 124.3, 119.0, 52.8, 24.8.

Example 3: HCNN-Bu ^t ligand producing 1- (benzo [h] quinolin-2-yl) -2,2-dimethyl propanone and _NH 2 OH-HCl were prepared by reacting (benzo [ h] Quinolin-2-yl) -t-butylketoxime was obtained by reduction using Zn.

1- (Benzo [h] quinolin-2-yl) -2,2-dimethylpropanone. A solution of 2-bromobenzo [h] quinoline (1.52 g, 5.89 mmol) in THF (36 ml) was cooled to −78 ° C. and after 10 minutes in n-hexane (2.47 ml, 6.18 mmol). Of 2.5M n-butyllithium was slowly added. The resulting dark red solution was stirred for 1 hour at this temperature, then a solution of 2,2-dimethylpropanonitrile (0.78 ml, 7.04 mmol) in THF (5 ml) was added dropwise. The solution was stirred at −78 ° C. for an additional hour and finally warmed slowly to ambient temperature. Then a solution of 1M H ₂ SO ₄ (25 ml, 25 mmol) was added and the mixture was heated at reflux for 3 hours. After cooling, the organic phase was separated and the aqueous phase was extracted with Et ₂ O (3 × 15 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography (eluent: petroleum ether / acetic acid = 9/1) and 1.24 g (80% yield) of 1- (benzo [h] quinolin-2-yl) -2,2 -Dimethylpropanone was obtained in the form of a yellow solid; melting point: 88-90 ° C.
Elemental analysis calculated for C ₁₈ H ₁₇ NO (%): C, 82.10; H, 6.51; N, 5.32. Detection: C, 82.10; H, 6.51; N, 5.32. ¹ H NMR (CDCl ₃ ): δ 9.20 (d, J = 7.8 Hz, 1H), 8.13 (s, 2H), 7.84 (d, J = 7.8 Hz, 1H), 7.80-7.73 (m, 2H), 7.73-7.62 (m, 1H), 7.56 (d, J = 9 Hz, 1H), 1.67 (s, 9H). ¹³ C { ¹ H} NMR (CDCl ₃ ): δ 206.7, 152.1, 144.5, 136.3, 133.7, 131.8, 129.5, 128.4, 127.9, 127.5 , 124.9, 124.5, 121.2, 44.3, 28.0.

1- (Benzo [h] quinolin-2-yl) -2,2-dimethylpropanone oxime. 1- (Benzo [h] quinolin-2-yl) -2,2-dimethylpropanone (1.30 g, 4.94 mmol) and hydroxylamine hydrochloride (0.63 g, 9.9) in 96% ethanol (45 ml). 07 mmol) was stirred at ambient temperature for 36 hours. The reaction was monitored by TLC (SiO ₂ ; eluent: petroleum ether / acetic acid = 9/1). The solvent was evaporated under reduced pressure and the residue was dissolved with CH ₂ Cl ₂ and saturated NaHCO ₃ solution. The resulting mixture was stirred vigorously for 30 minutes and then the organic phase was separated. The aqueous phase was extracted with CH ₂ Cl ₂ (2 × 20 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated to give 0.69 g (50% yield) of 1- (benzo [h] quinolin-2-yl) -2,2-dimethyl. The propanone oxime was obtained in the form of a light brown solid and was used in the next step without further purification: mp 234-236 ° C.
Elemental analysis calculated for C ₁₈ H ₁₈ N ₂ O (%): C, 77.67; H, 6.52; N, 10.06. Detection: C, 77.55; H, 6.55; N, 10.02.

1- (Benzo [h] quinolin-2-yl) -2,2-dimethylpropanamine. The oxime of 1- (benzo [h] quinolin-2-yl) -2,2-dimethylpropanone (1.30 g, 4.67 mmol) in a mixture consisting of 30% NH ₃ / H ₂ O / 96% EtOH and A solution of ammonium acetate (0.447 g, 5.80 mmol) was stirred for 30 minutes at ambient temperature. Over a period of 2 hours (at room temperature), zinc in powder form (1.68 g, 25.7 mmol) was added and the resulting mixture was heated at reflux for 4 hours. After cooling, the mixture was treated with an aqueous solution of 36% HCl to pH = 1 and concentrated under reduced pressure. The residue was treated with an aqueous solution of 50% KOH and the solution was extracted with Et ₂ O (4 × 25 ml). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography using MeOH as eluent to give 1- (benzo [h] quinolin-2-yl) -2,2-dimethylpropanamine in the form of an orange oil: 0. 59 g (48% yield).
Elemental analysis calculated for C ₁₅ H ₂₀ N ₂ : C, 81.78; H, 7.63; N, 10.60. Detection: C, 81.66; H, 7.67; N, 10.63. ¹ H NMR (CDCl ₃ ): δ 9.31 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 7.5 Hz, 1H), 7.76-7.55 (m, 4H), 7.34 (d, J = 8.1 Hz, 1H), 3.88 (s, 1H), 2.65 (s, 2H), 0.99 (s, 9H). ¹³ C { ¹ H} NMR (CDCl ₃ ): δ 161.1, 145.1, 134.8, 133.4, 131.4, 127.8, 127.5, 126.8, 126.6, 125.0, 124.8, 124.3, 122.2, 65.8, 35.5, 26.5.

Example 4: Synthesis of complex [RuCl (PPh ₃ ) ₂ (CNN-H)] (6) Complex RuCl ₂ (PPh ₃ ) ₃ (4) suspended in 2 ml distilled toluene (0.150 g, 0.156 mmol) ) Was reacted with HCNN-H (1) (36 mg, 0.174 mmol) and triethylamine (0.22 ml, 0.158 mmol). After stirring the mixture for 2 hours at 110 ° C., the solution volume was approximately halved and the complex was precipitated by adding 2 ml of pentane. The resulting solid was filtered, washed with pentane (3 × 5 ml) and dried under reduced pressure. Yield 100 mg (74%).
Elemental analysis calculated for C ₅₀ H ₄₁ ClN ₂ P ₂ Ru (%). C, 69.16; H, 4.76; N, 3.23. Detection: C, 69.35; H, 4.85; N, 3.34. ³¹ P { ¹ H} NMR (81.0 MHz, CD ₂ Cl ₂ , 20 ° C, H ₃ P0 ₄ ): δ 56.5 (d, J (PP) = 33.4 Hz), 50.5 (d, J (PP) = 33.4 Hz).

Example 5: Complex _{RuCl [PPh 2 (CH 2)} 4 PPh 2] (CNN-H) HCNN-H (1) Synthesis of 2-propanol (15ml) of (7) ligand (232 mg, 1.11 mmol) and To a solution of triethylamine (1.55 ml, 11.1 mmol), the complex RuCl ₂ (PPh ₃ ) [PPh ₂ (CH ₂ ) ₄ PPh ₂ ] (5) (800 mg, 0.929 mmol) was added. The mixture was refluxed for 2 hours and the resulting orange precipitate was filtered, washed with methanol (3 × 10 ml) and dried under reduced pressure. Yield 608 mg (85%).
Elemental analysis calculated for C ₄₂ H ₃₉ ClN ₂ P ₂ Ru (%): C, 65.49; H, 5.10; N, 3.64. Detection: C, 65.18; H, 5.23; N, 3.47. ¹ H NMR (200.1 MHz, CD ₂ Cl ₂ , 20 ° C, TMS): δ 8.19 (pseudo t, J (HH) = 7.6 Hz, 2H; aromatic proton), 7.99 (d, J (HH) = 7.0 Hz, 1H; aromatic proton), 7.82 (pseudo-t, J (HH) = 8.0 Hz, 2H; aromatic proton), 7.64 (d, J (HH) = 8.5 Hz, 2H; aromatic proton), 7.52-7.20 ( m, 14H; aromatic proton), 6.98 (d, J (HH) = 8.2 Hz, 1H; aromatic proton), 6.45 (t, J (HH) = 7.3 Hz, 1H; aromatic proton), 6.16 (pseudo t, J (HH) = 7.8 Hz, 2H; aromatic proton), 5.47 (t, J (HH) = 8.1 Hz, 2H; aromatic proton), 4.37 (dd, J (HH) = 16.3, 5.4 Hz, 1H; CH ₂ N), 3.96 (ddd, J (HH) = 16.4, 11.0, 5.0 Hz, 1H; CH ₂ N), 3.60 (m, 1H; NH ₂ ), 3.01 (m, 2H; CH ₂ ), 2.35-1.00 (m, 7H; CH ₂ + NH ₂ ). ¹³ C { ¹ H} NMR (50.3 MHz, CDCl ₃ , 20 ° C, TMS): δ 177.0 (dd; J (CP) = 16.6, 8.3 Hz ; CRu), 154.3 (s; NCC), 152.3 ( d, J (CP) = 1.0 Hz; NCCH ₂ ), 146.2-115.5 (m; aromatic carbon), 52.2 (d, J (CP) = 2.8 Hz; CH ₂ N), 33.1 (dd, J (CP) = 24.8, 1.8 Hz; CH ₂ ), 29.9 (d, J (CP) = 31.9 Hz; CH ₂ ), 26.5 (d, J (CP) = 1.3 Hz; CH ₂ ), 21.5 (dd, J (CP) _{= 2.5, 2.0 Hz; CH 2} ) 31 P {1 H} NMR. (81.0 MHz, CD 2 Cl 2, 20 ° C, H 3 P0 4): δ 57.3 (d, J (PP) = 38.2 Hz), 43.7 (d, J (PP) = 38.2 Hz).

Example 6: Complex _{RuH [PPh 2 (CH 2)} 4 PPh 2] (CNN-H) complex RuCl in synthetic <br/> toluene (2.9 ml) of _{(8) [PPh 2 (CH} 2) 4 PPh 2 ] (CNN-H) (7 ) (150mg, 0.195mmol) was suspended, it was added a solution of 2-propanol ^{0.1M NaO i Pr (2.9ml, 0.202mmol} ). The mixture was stirred at 60 ° C. for 1 hour. The resulting dark red solution was concentrated to half volume, stirred for 1 hour at room temperature (RT), and after addition of toluene (3 mL), held at -20 ° C. for 18 hours to obtain a NaCl precipitate. , Filtered through celite (raw glass raw material). The solution was stirred for 1 hour at room temperature under H ₂ (1 atm) and the solvent was removed to give a bright orange product which was dried under reduced pressure. Yield 119 mg (83%).
Elemental analysis calculated for C ₄₂ H ₄₀ N ₂ P ₂ Ru (%): C, 68.56; H, 5.48; N, 3.81. Detection: C, 68.20; H, 5.44; N, 3.45. ¹ H NMR (200.1 MHz, C ₆ D ₆ , 20 ° C, TMS): δ 8.58 (t, J (HH) = 8.2 Hz, 2H; aromatic proton), 8.40-6.80 (m, 18H; aromatic proton), 6.37 (d , J (HH) = 6.8 Hz, 1H; aromatic proton), 6.27 (d, J (HH) = 7.7 Hz, 2H; aromatic proton), 6.14 (m, 2H; aromatic proton), 5.50 (t, J (HH) = 6.5 Hz, 2H; aromatic proton), 3.20-1.45 (m, 12H; CH ₂ , NH ₂ ),-5.40 (dd, J (HP) = 90.0, 26.2 Hz, 1H; Ru-H ³¹ P { ¹ H} NMR (81.0 MHz, C ₆ D ₆ , 20 ° C, H ₃ PO ₄ ): δ 66.6 (d, J (PP) = 16.7 Hz), 35.0 (d, J (PP) = 16.7 Hz) .IR (Nujol) v ~ = 1741.6 cm ^-1 (br. Ru-H).

Example 7: Complex _{Ru [O-CH (p-} C 6 H 4 F) 2] [PPh 2 (CH 2) 4 PPh 2] (CNN-H) Synthesis <br/> toluene (9) (3.9 ml ) And the complex RuCl [PPh ₂ (CH ₂ ) ₄ PPh ₂ ] (CNN-H) (7) (200 mg, 0.260 mmol) suspended in 0.1 M NaO ⁱ Pr (3.9 ml in 2-propanol). , 0.390 mmol) was added. The suspension was stirred at 60 ° C. for 2 hours. The resulting dark red mixture was stirred for 1 hour at ambient temperature, then cooled to −20 ° C. for 24 hours to promote NaCl precipitation and removed by filtration through celite (fine-grained glass raw material). To the solution was added 4,4′-difluorobenzophenone (68.0 mg, 0.312 mmol) and then stirred at ambient temperature for 30 minutes. The solvent was removed by evaporation under reduced pressure and the residue was treated with toluene (2 ml). The mixture was maintained at −20 ° C. for 2 hours, filtered through celite (fine-grained glass raw material), and the filtrate was concentrated to about 1 ml. Addition of pentane resulted in the precipitation of an orange-red product, which was collected by filtration and dried under reduced pressure. Yield 186 mg (75%).
C ₅₅ H ₄₈ F ₂ N calculated elemental analysis of _{2 OP 2 Ru (%):} . C, 69.24; H, 5.07; N, 2.94 Detection:. C, 69.16; H, 5.29; N, 2.93 1 H NMR (200.1 MHz, C ₆ D ₆ , 20 ° C, TMS): δ 8.15 (m, 2H; aromatic proton), 8.03 (t, J (HH) = 7.60 Hz, 2H; aromatic proton), 7.66-6.25 (m, 26H; aromatic proton), 6.02 (t, J (HH) = 7.8 Hz, 2H; aromatic proton), 5.86 (d, J (HH) = 8.0 Hz, 1H; aromatic proton), 5.41 ( t, J (HH) = 8.2 Hz, 2H; aromatic proton), 5.28 (width s, 1H; NH ₂ ), 4.46 (d, J (HP) = 3.3 Hz, 1H; OCH), 3.24-2.65 (m , 4H; CH ₂ , NH ₂ ), 2.35-0.80 (m, 7H; CH ₂ , NH ₂ ). ¹³ C { ¹ H} NMR (50.3 MHz, C ₆ D ₆ , 20 ° C, TMS): δ 183.4 (dd; J (CP) = 15.0, 8.5 Hz, CRu), 161.1 (d, J (CF) = 240.6 Hz; CF), 160.6 (d, J (CF) = 240.2 Hz; CF), 156.0-113.4 ( m; aromatic carbon), 79.9 (s, OCH), 52.0 (d, J (CP) = 2.5 Hz; CH ₂ N), 31.3 (d, J (CP) = 28.3 Hz; CH ₂ P), 30.7 ( d, J (CP) = 29.5 Hz; CH ₂ P), 26.8 (s; CH ₂ ), 22.3 (d, J (CP) = 2.3 Hz; CH ₂ ). ³¹ P { ¹ H} NMR (81.0 MHz, C ₆ D ₆ , 20 ° C, H ₃ PO ₄ ): δ 57.0 (d, J (PP) = 34.3 Hz), 40.3 (d, J (PP) = 34.3 Hz ¹⁹ F { ¹ H} NMR (188.3 MHz, C ₆ D ₆ , 20 ° C): δ -119.6, -120.3.

Example 8: Synthesis 3 hours reflux the complex _{RuCl [PPh 2 (CH 2)} 4 PPh 2] (CNN-Me) (10), complex in 2-propanol _{2ml RuCl 2 [PPh 2 (CH} 2) 4 _{PPh 2] (PPh 3) (} 5) (0.100g, 0.116mmol), HCNN-Me (2) (39mg, 0.175mmol) and triethylamine (0.16 ml, 1.15 mmol) was heated. The precipitate obtained by addition of pentane was filtered and washed with pentane (4 × 3 ml). The solid was suspended in dichloromethane (0.5 ml) and kept at −20 ° C. overnight. After filtration, the volume of the solution was reduced to 1/2 and pentane (2 ml) was added. The resulting precipitate was filtered, washed with 2 ml of pentane and dried under reduced pressure. Yield: 60 mg (66%).
Elemental analysis calculated for C ₄₃ H ₄₁ ClN ₂ P ₂ Ru (%): C, 65.85; H, 5.27; N, 3.57; detection C, 66.10; H, 5.40; N, 3.74. ¹ H NMR (200.1 MHz , CD ₂ Cl ₂ , 20 ° C, TMS): δ 8.18 (pseudo-t, J (HH) = 8.0 Hz, 2H; aromatic proton), 8.01 (d, J (HH) = 7.0 Hz, 1H; aromatic Proton), 7.82 (pseudo t, J (HH) = 8.4 Hz, 2H; aromatic proton), 7.68 (d, J (HH) = 5.4 Hz, 1H; aromatic proton), 7.65 (d, J (HH) = 6.0 Hz, 1H; aromatic proton), 7.49-7.22 (m, 14H; aromatic proton), 6.98 (d, J (HH) = 8.4 Hz, 1H; aromatic proton), 6.45 (t, J (HH ) = 7.4 Hz, 1H; aromatic proton), 6.16 (pseudo t, J (HH) = 8.2 Hz, 2H; aromatic proton), 5.45 (t, J (HH) = 8.4 Hz, 2H; aromatic proton) , 4.37 (m, 1H; CHMeN), 3.55 (t, J (HH) = 11.4 Hz, 1H; NH ₂ ), 3.20-2.85 (m, 3H; CH ₂ ), 2.40-1.70 (m, 6H; CH _{2 + NH 2), 1.58 (d} , J (HH) = 6.7 Hz, 3H; CMe) 13 C {1 H} NMR (50.3 MHz, CD 2 Cl 2, 20 ° C):. δ 179.1 (dd, J ( CP) = 16.3, 8.4 Hz; CRu), 15 7.8-116.5 (m; aromatic carbon), 58.5 (d, J (CP) = 2.6 Hz; CHN), 33.3 (dd, J (CP) = 24.9, 2.2 Hz; CH ₂ P), 30.5 (d, J (CP) = 32.1 Hz; CH ₂ P), 26.8 (d, (CP) = 2.0 Hz; CH ₂ ), 23.4 (s; Me), 22.0 (m, Hz; CH ₂ ). ³¹ P { ¹ H} NMR (81.0 MHz, CD ₂ Cl ₂ , 20 ° C, H ₃ P0 ₄ ): δ 57.3 (d, J (PP) = 38.3 Hz), 43.6 (d, J (PP) = 38.3 Hz).

Example 9: Complex _{RuCl [PPh 2 (CH 2)} 4 PPh 2] (CNN- t Bu) Synthesis of (11) <br/> complexes _{RuCl 2 [PPh 2 (CH 2} ) 4 PPh 2] (PPh 3) ( 5) (0.100 g, 0.116 mmol), HCNN- ^t Bu (3) (46 mg, 0.174 mmol) and triethylamine (0.16 ml, 1.15 mmol) were added to 2 ml 2-propanol and refluxed for 5 hours did. The solution was then concentrated and the precipitate obtained by addition of pentane was filtered, washed with pentane (4 × 3 ml) and dried under reduced pressure. The solid was suspended in dichloromethane (0.5 ml) and kept at −20 ° C. overnight. After filtration, the volume of the solution was reduced to ½ and pentane (2 ml) was added. The precipitate was filtered, washed with 2 ml of pentane and dried under reduced pressure. Yield: 50 mg (52%).
Elemental analysis calculated for C ₄₆ H ₄₇ ClN ₂ P ₂ Ru (%): C, 66.86; H, 5.73; N, 3.39; detection C, 67.10; H, 5.70; N, 3.19. ¹ H NMR (200.1 MHz , CD ₂ Cl ₂ , 20 ° C, TMS): δ 8.08 (pseudo-t, J (HH) = 9.5 Hz, 2H; aromatic proton), 7.98 (d, J (HH) = 6.9 Hz, 1H; aromatic Proton), 7.71 (pseudo-t, J (HH) = 8.4 Hz, 2H; aromatic proton), 7.53 (d, J (HH) = 8.7 Hz, 1H; aromatic proton), 7.51 (d, J (HH) = 8.5 Hz, 1H; aromatic proton), 7.39-7.19 (m, 14H; aromatic proton), 7.11 (d, J (HH) = 8.8 Hz, 1H; aromatic proton), 6.33 (pseudo-t, J ( HH) = 8.0 Hz, 1H; aromatic proton), 6.03 (pseudo-t, J (HH) = 8.0 Hz, 2H; aromatic proton), 5.32 (t, J (HH) = 8.4 Hz, 2H; aromatic proton ), 3.60-3.36 (m, 2H; CH ^t BuN + NH ₂ ), 3.09-2.84 (m, 3H; CH ₂ ), 2.24-1.40 (m, 6H; CH ₂ + NH ₂ ), 0.91 (s, 9H ^t Bu). ¹³ C { ¹ H} NMR (50.3 MHz, CD ₂ Cl ₂ , 20 ° C): δ 180.3 (dd, J (CP) = 16.7, 8.1 Hz; CRu), 155.5-118.8 (m; Aromatic carbon), 7 2.9 (s; d, J (CP) = 2.9 Hz; CHN), 35.3 (s; CMe ₃ ), 33.4 (dd, J (CP) = 24.7, 1.9 Hz; CH ₂ P), 30.4 (d, (CP ) = 32.2 Hz; CH ₂ P), 27.5 (s; Me), 27.0 (d, J (CP) = 1.7 Hz; CH ₂ ), 21.8 (d, J (CP) = 3.1 Hz; CH ₂ ). ³¹ P { ¹ H} NMR (81.0 MHz, CD ₂ Cl ₂ , 20 ° C, H ₃ P0 ₄ ): δ 57.1 (d, J (PP) = 38.6 Hz), 44.5 (d, J (PP) = 38.6 Hz ).

Example 10: Synthesis of complex RuCl [(R, S) -Josiphos] (CNN-H)) (12) [RuCl ₂ (PPh ₃ ) ₃ ] (4) ( 0.150 g , 0.156 mmol) and (R, Toluene (2 ml) was added to S) -Josiphos-C ₂ H ₅ OH (120 mg, 0.187 mmol) and the suspension was refluxed for 1 hour. The solvent was removed under reduced pressure and the residue was treated with 2-propanol (2 ml), ligand HCNN-H (1) (36 mg, 0.172 mmol) and NEt ₃ (0.22 ml, 1.58 mmol). The mixture was refluxed for 2 hours and then cooled to room temperature. Addition of pentane (5 ml) gave a precipitate, which was filtered, washed with pentane (4 × 3 ml) and dried under reduced pressure. The solid was dissolved in CH ₂ Cl ₂ (0.5 ml) and maintained at −20 ° C. for 18 hours to give a precipitate of triethylammonium chloride which was removed by filtration. The solution was concentrated (1 ml) and an orange precipitate was obtained by addition of pentane (2 ml), filtered, washed with pentane (2 × 2 ml) and dried under reduced pressure. Yield: 90 mg (61%).
_{C 50 H 55 ClFeN 2 P 2} Ru calculated elemental analysis (%):. C, 64.00 ; H, 5.91; N, 2.99; detection C, 64.30; H, 6.02; N, 3.05 1 H NMR (200.1 MHz , CD ₂ Cl ₂ , 20 ° C, TMS): δ 8.33 (d, J (HH) = 7.0 Hz, 1H; aromatic proton), 8.22-7.16 (m, 16H; aromatic proton), 4.70-4.35 ( m, 4H; FeCH + CHP), 4.24-4.10 (m, 2H; CH ₂ N), 3.79 (s, 5H; C ₅ H ₅ ), 3.45 (m, 1H; NH ₂ ), 2.95-0.60 (m, 26H; CH + CH ₂ + CH ₃ + NH ₂ ). ¹³ C { ¹ H} NMR (50.3 MHz, CD ₂ Cl ₂ , 20 ° C): δ 158.0-117.0 (m; aromatic carbon), 74.4 (s ; FeC ₅ H ₃ ), 70.8 (s; FeC ₅ H ₅ ), 70.3 (d, J (CP) = 4.3 Hz; FeC ₅ H ₃ ), 68.9 (d, J (CP) = 4.8 Hz; FeC ₅ H ₃ ), 53.0 (d, J (CP) = 1.8 Hz; CHNH ₂ ) 40.4 (d, J (CP) = 15.8 Hz; CH of Cy), 38.0 (d, J (CP) = 17.5 Hz; CH of Cy ), 31.8-23.1 (m; CH ₂ of Cy), 29.6 (d, J (CP) = 3.5 Hz; PCMe), 15.9 (d, J (CP) = 6.8 Hz; PCMe). ³¹ P { ¹ H} NMR (81.0 MHz, CDCl ₃ , 20 ° C, H ₃ P0 ₄ ): δ 68.8 (d, J (PP) = 42.0 Hz), 43.4 (d, J (PP) = 42.0 Hz).

Example 11: Synthesis of complex RuCl [(S, R) -Josiphos ^* ] (CNN-H) (13) (mixture of three diastereomers in a ratio of 1: 0.06: 0.20)
The complex RuCl ₂ (PPh ₃ ) ₃ (4) (0.150 g, 0.156 mmol) was reacted with (S, R) -Josiphos ^* (133 mg, 0.187 mmol) in 2 ml of dichloromethane for 1 hour. The solvent was then removed and HCNN-H (1) (36 mg, 0.172 mmol), triethylamine (0.22 ml, 1.58 mmol) and 2 ml of 2-propanol / heptane (1: 1) mixture were added. The resulting mixture was refluxed overnight (110 ° C.). The resulting solid (NEt ₃ HCl) was filtered, the solvent was removed, heptane (2 ml) was added and the resulting solution was maintained under reflux for 2 hours. The solution volume was then reduced to ½ and 1 ml of pentane was added. The precipitate was filtered, washed with pentane (3 × 2 ml) and dried under reduced pressure. The solid was suspended in dichloromethane (0.5 ml) and kept at −20 ° C. overnight. After filtration, the solution volume was reduced to 1/2 and pentane (2 ml) was added. The precipitate was filtered, washed with pentane (2 × 2 ml) and dried under reduced pressure. Yield: 90 mg (55%).
Elemental analysis calculated for C ₅₆ H ₆₇ ClFeN ₂ O ₂ P ₂ Ru (%): C, 63.79; H, 6.40; N, 2.66; detection C, 64.02; H, 6.60; N, 2.86. ³¹ P { ¹ H} NMR (81.0 MHz, CD ₂ Cl ₂ , 20 ° C, H ₃ P0 ₄ ): δ 67.3 (d, J (PP) = 41.9 Hz), 38.5 (d, J (PP) = 41.9 Hz) 60.1 (d, J (PP) = 40.0 Hz), 40.9 (d, J (PP) = 40.0 Hz); 64.4 (d, J (PP) = 34.5 Hz), 56.1 (d, J (PP) = (34.5 Hz) By-product.

Example 12: Synthesis of complex RuCl [(S, S)-(-)-Skewphos] (CNN) (14) (mixture of two diastereomers in a ratio of 1: 0.23)
The complex RuCl ₂ (PPh ₃ ) ₃ (4) (0.150 g, 0.156 mmol) was reacted with (S, S)-(−)-Skewphos (89 mg, 0.202 mmol) in 3 ml of toluene. The suspension was refluxed for 2 hours, the toluene was evaporated and HCNN-H (1) (36 mg, 0.172 mmol), triethylamine (0.22 ml, 1.58 mmol) and 2-propanol (2 ml) were added. The mixture was then heated again at reflux (110 ° C.) for 2 hours. The precipitate obtained by addition of pentane was filtered and washed with pentane (3 × 3 ml). The solid was suspended in dichloromethane (0.5 ml) and kept at −20 ° C. overnight. After filtration, the solution volume was reduced to 1/2 and pentane (2 ml) was added. The precipitate was filtered, washed with pentane (1 × 2 ml) and dried under reduced pressure. Yield 70 mg (57%).
_{C 43 H 41 ClN 2 P 2} Ru calculated elemental analysis (%):. C, 65.85 ; H, 5.27; N, 3.57; detection C, 66.06; H, 5.37; N, 3.63 1 H NMR (200.1 MHz , CD ₂ Cl ₂ , 20 ° C, TMS): δ 8.31-5.80 (m, 27H; aromatic proton), 4.42 (s), 4.20 (d, J (HH) = 3.4 Hz), 3.68 (s width) , 3.37 (m), 3.03 (m), 2.78 (s width), 2.36 (q, J (HH) = 13.5 Hz), 2.00-1.40 (m), 1.35 (t, J (HH) = 7.4 Hz), 1.29 (dd, J (HP), J (HH) = 14.5, 7.3 Hz), 0.91 (m width), 0.76 (s width), 0.55 (dd, J (HP), J (HH) = 6.9, 11.4 Hz ¹³ C { ¹ H} NMR (50.3 MHz, CD ₂ Cl ₂ , 20 ° C): δ 178.5 (m; CRu), 159.3-116.2 (m; aromatic carbon), 51.3 (d, J (CP) = 1.5 Hz; CH ₂ N), 37.9 (m; CH ₂ ), 33.0 (m; PCH), 32.6 (m; PCH), 20.1 (s; CH ₃ ), 19.5 (d, J (CP) = 6.1 Hz _{; CHCH 3) 17.5 (d,} J (CP) = 6.5 Hz; CHCH 3) 31 P {1 H} NMR (81.0 MHz, CD 2 Cl 2, 20 ° C, H 3 P0 4):. δ 66.2 (d , J (PP) = 46.1 Hz), 47.8 (d, J (PP) = 46.2 Hz), main product; 64.4 (d, J (PP) = 48.7 Hz), 53.3 (d, J (PP) = 48.7 Hz).

Example 13: Synthesis of complex RuCl [(S) -MeO-Biphep] (CNN-H) (15) (mixture of two diastereomers in a ratio of 1: 0.18)
The complex RuCl ₂ (PPh ₃ ) ₃ (4) (0.150 g, 0.156 mmol) and S-MeO-Biphep (136 mg, 0.233 mmol) were refluxed in 2 ml toluene for 1 hour, after which the toluene was Evaporated and HCNN-H (1) (36 mg, 0.172 mmol), triethylamine (0.22 ml, 1.58 mmol) and 2-propanol (2 ml) were added. The mixture was then heated at reflux (110 ° C.) for 2 hours. The precipitate obtained by addition of pentane was filtered and washed with pentane (4 × 3 ml). The solid was suspended in dichloromethane (0.5 ml) and kept at −20 ° C. overnight. After filtration, the solution volume was reduced to ½ and pentane was added (2 ml). The precipitate was filtered, washed with pentane (2 × 2 ml) and dried under reduced pressure. Yield: 95 mg (66%).
Elemental analysis calculated for C ₅₂ H ₄₃ ClN ₂ O ₂ P ₂ Ru (%): C, 67.42; H, 4.68; N, 3.02; detection C, 67.93; H, 4.80; 3.12; ¹ H NMR (200.1 MHz , CDCl ₃ , 20 ° C, TMS): δ 8.45 (d, J (HH) = 7.0 Hz), 8.07-5.52 (m; aromatic proton), 4.43 (dd, J (HH) = 15.8, 5.4 Hz; CH ₂ ), 4.25 (m), 3.88 (s; OMe), 3.74 (s; OMe), 3.39 (s; OMe), 3.28 (s; OMe), 2.05 (t, J (HH) = 7.3 Hz; NH ₂ ). ¹³ C { ¹ H} NMR (50.3 MHz, CDCl ₃ , 20 ° C, TMS): δ 177.8 (m; CRu), 164.8-110.6 (m; aromatic carbon), 55.8 (s, OCH ₃ ) , 55.7 (s, OCH ₃ ), 54.9 (s, OCH ₃ ), 54.6 (s, OCH ₃ ), 52.2 (d, J (CP) = 1.7 Hz; CH ₂ ). ³¹ P { ¹ H} NMR (81.0 MHz, CD ₂ Cl ₂ , 20 ° C, H ₃ P0 ₄ ): δ 50.3 (d, J (PP) = 35.5 Hz), 49.8 (d, J (PP) = 35.5 Hz), main product; 60.3 ( d, J (PP) = 40.5 Hz), 51.9 (d, J (PP) = 40.5 Hz).

Example 14: complex _{OsCl [PPh 2 (CH 2)} 4 PPh 2] (CNN-H) Synthesis <br/> complex OsCl _{2 (PPh 3)} of (7a) 3 (4a) ( 200mg, 0.191mmol) and bis (1,4-Diphenylphosphino) butane (98 mg, 0.230 mmol) was dissolved in anhydrous CH ₂ Cl ₂ (5 ml) to give a green solution that was stirred at ambient temperature for 2 hours. The solvent was evaporated under reduced pressure and the residue was suspended in 2-propanol (5 ml), where HCNN-H ligand (1) (48 mg, 0.230 mol) and triethylamine (0.32 ml, 2. 30 mmol) was added. The mixture was then refluxed for 3 hours, filtered and washed with 2-propanol (3 × 10 ml) and pentane (2 × 10 ml) to give a red precipitate. The product was dried overnight at 45 ° C. under reduced pressure. Yield 144 mg (88%).
Elemental analysis calculated for C ₄₂ H ₃₉ ClN ₂ OsP ₂ (%): C, 58.70; H, 4.57; N, 3.26. Detection: C, 58.42; H, 4.74; N, 3.27. ¹ H NMR (200.1 MHz , CD ₂ Cl ₂ , 20 ° C, TMS): δ 8.13 (pseudo t, J (HH) = 7.5 Hz, 2H; aromatic proton), 7.93 (d, J (HH) = 6.9 Hz, 1H; aromatic Proton), 7.76 (t, J (HH) = 7.5 Hz, 2H; aromatic proton), 7.64-7.20 (m, 16H; aromatic proton), 6.98 (d, J (HH) = 8.1 Hz, 1H; aromatic Group proton), 6.44 (t, J (HH) = 7.3 Hz, 1H; aromatic proton), 6.17 (pseudo t, J (HH) = 7.8 Hz, 2H; aromatic proton), 5.49 (t, J (HH ) = 7.9 Hz, 2H; aromatic proton), 4.50 (d, J (HH) = 20.7 Hz, 1H; CH ₂ NH ₂ ), 4.00 (m, 2H; NH ₂ , CH ₂ NH ₂ ), 3.53 (m , 1H; CH ₂ ), 3.30-2.65 (m, 2H; CH ₂ , NH ₂ ), 2.42-1.48 (m, 6H; CH ₂ ). ¹³ C { ¹ H} NMR (50.3 MHz, CD ₂ Cl ₂ , 20 ° C, TMS): δ 157.2 (t; J (CP) = 6.5 Hz; C-Os), 155.6 (s; NCC), 154.5 (s; NCCH ₂ ), 147.7-115.8 (m; aromatic carbon) , 54.6 (s; CH ₂ N), 35.2 (dd, J (CP) = 36.5, 4. 3 Hz; CH ₂ ), 30.2 (dd, J (CP) = 42.2, 5.2 Hz; CH ₂ ), 26.7 (s; CH ₂ ), 21.2 (t, J (CP) = 2.0 Hz; CH ₂ ). ³¹ P { ¹ H} NMR (81.0 MHz, CD ₂ Cl ₂ , 20 ° C, H ₃ PO ₄ ): δ 0.9 (d, J (PP) = 13.7 Hz), 0.8 (d, J (PP) = 13.7 Hz ).

Example 15: complex _{OsH [PPh 2 (CH 2)} 4 PPh 2] (CNN-H) in the synthesis of 2-propanol (8a) NaOiPr (1.3ml, 0.130mmol ) and 0.1M solution of toluene ( To the suspension of the complex of Example 14 (7a) (100 mg, 0.116 mmol) in 1.3 ml) and the mixture was stirred for 3 hours at 35 ° C. The resulting dark red solution was maintained at −20 ° C. for 4 hours to obtain a NaCl precipitate, which was filtered through celite (fine glass raw material). The solvent was removed at low pressure and the solid was extracted with pentane (1 ml) to give a brown product dried under reduced pressure. Yield: 71 mg (74%).
C ₄₂ H ₄₀ N ₂ OsP ₂ calculated elemental analysis (%): C 61.15, H 4.89, N 3.40; detection:. C 60.85, H 5.02, N 3.13 1 H NMR (200.1 MHz, C 6 D 6, 20 ° C): δ = 8.53 (t, J (H, H) = 8.5 Hz, 2H; aromatic proton), 8.31 (d, J (H, H) = 7.9 Hz, 1H; aromatic proton), 8.05 -6.62 (m, 18H; aromatic proton), 6.40 (t, J (H, H) = 8.2 Hz, 1H; aromatic proton), 6.25-6.05 (m, 3H; aromatic proton), 5.49 (t, J (H, H) = 7.6 Hz, 2H; aromatic proton), 4.0 (t, J (H, H) = 6.9 Hz, 1H; NCH ₂ ), 3.66-0.70 (m, 11H; CH ₂ , NH ₂ ), -5.14 ppm (dd, ² J (H, P) = 73.9, 23.9 Hz, 1H; OsH); ³¹ P { ¹ H} NMR (81.0 MHz, C ₆ D ₆ , 20 ° C): δ = 19.9 (d, ² J (P, P) = 3.7 Hz), 5.4 ppm (d, ² J (P, P) = 3.7 Hz).

Example 16: complex _{Os [O-CH (p-} C 6 H 4 F) 2] [PPh 2 (CH 2) 4 PPh 2] (CNN-H) (9a) NaOiPr in the synthesis of 2-propanol (1. 6 ml, 0.160 mmol) in 0.1 M solution was added to a suspension of the complex of Example 14 (7a) (123 mg, 0.143 mmol) in toluene (1.6 ml) and the mixture was allowed to reach 35 ° C. for 3 hours. Was stirred at. The resulting dark red solution was maintained at −20 ° C. for 4 hours to obtain a NaCl precipitate, which was filtered through celite (fine-grain glass raw material). 4,4′-Difluorobenzophenone (35 mg, 0.160 mmol) was added and the mixture was stirred for 1 hour at room temperature. The solvent was removed, toluene (2 ml) was added and the mixture was maintained at −20 ° C. for 2 hours, filtered over celite, and the solution was concentrated. Addition of pentane (5 ml) gave a dark yellow product precipitate which was filtered and dried under reduced pressure. Yield: 107 mg (72%).
_{C 55 H 48 F 2 N 2} OOsP 2 calculated elemental analysis (%): C 63.33, H 4.64, N 2.69; detection:. C 62.84, H 4.72, N 2.62 1 H NMR (200.1 MHz, C 6 D ₆ , 20 ° C): δ = 8.18 (t, J (H, H) = 7.5 Hz, 1H; aromatic proton), 8.07 (d, J (H, H) = 8.3 Hz, 1H; aromatic proton) , 7.93 (t, J (H, H) = 7.6 Hz, 2H; aromatic proton), 7.66-6.21 (m, 26H; aromatic proton), 6.04 (dt, J (H, H) = 7.6, 1.8 Hz , 2H; aromatic proton), 5.83 (d, J (H, H) = 8.2 Hz, 1H; aromatic proton), 5.42 (t, J (H, H) = 7.9 Hz, 2H; aromatic proton), 5.28 (width s, 1H; NH ₂ ), 4.61 (m, 1H; OCH), 3.48 (m, 1H; NCH ₂ ), 3.26 (s, 2H; CH ₂ and NH ₂ ), 2.91 (pseudo t, J ( H, H) = 13.2 Hz, 1H; NCH ₂ ), 2.42 (m, 1H; CH ₂ ), 2.25 (m, 2H; CH ₂ ), 1.94-0.77 ppm (m, 4H; CH ₂ ); ¹³ C { ¹ H} NMR (50.3 MHz, C ₆ D ₆ , 20 ° C): δ = 162.4 (width d, ¹ J (C, F) = 245 Hz; CF), 162.0 (dd, ² J (C, P) = 7.9, 3.7 Hz; C-Os), 156.4 (s; CCN), 155.1 (s; NCCH ₂ ), 147.9-113.0 (m; aromatic carbon source Child), 79.7 (width s; OCH), 54.0 (d, ³ J (C, P) = 2.2 Hz; NCH ₂ ), 33.7 (d, ² J (C, P) = 33.2 Hz; PCH ₂ ), 30.8 (d, ² J (C, P) = 34.4 Hz; PCH ₂ ), 26.7 (s; CH ₂ ), 21.6 ppm (s; CH ₂ ); ³¹ P { ¹ H} NMR (81.0 MHz, C ₆ D ₆ , 20 ° C): δ = 1.8 (d, ² J (P, P) = 8.2 Hz), -0.8 ppm (d, ² J (P, P) = 8.2 Hz); ¹⁹ F { ¹ H} NMR ( 188.3 MHz, C ₆ D ₆ , 20 ° C): δ = -119.4, -120.1 ppm.

B. Catalytic test The ruthenium (II) and osmium (II) complexes of the present invention can be used to produce alcohols from the corresponding ketones by hydrogen transfer and hydrogenation reactions. In the presence of novel ruthenium and osmium based catalysts and alkali metal alkoxides, cyclic ketones, linear dialkyl ketones, alkyl aryl ketones and diaryl ketones R ⁶ C (═O) R ⁷ , wherein R ⁶ and R ⁷ represents a saturated or unsaturated aliphatic group), or a different alcohol by reduction of an aromatic hydrocarbon group which may or may not have a substituted alkyl group, an oxygen-containing substituent, a halogen atom or a heterocyclic group. It is possible to obtain.

A reduction reaction by hydrogen transfer was carried out in 2-propanol under reflux at a substrate / catalyst ratio comprised between 1000 and 100,000 in the presence of 2 mol% alkali metal alkoxide with respect to the substrate. It should be noted that the acetone produced by oxidation of 2-propanol can be separated from the reaction mixture by exploiting the lower boiling point relative to 2-propanol. Catalytic tests conducted in methanol at 40 ° C. against ruthenium complexes and at 70 ° C. against osmium complexes under a hydrogen atmosphere at low pressure (4-5 atm) are also defined and under the above conditions It is understood that there is a complete conversion of the ketone to the alcohol, thus demonstrating that these complexes are active in hydrogenation reactions using molecular hydrogen.

B1. Catalytic testing of hydrogen transfer and hydrogenation using non-chiral catalysts
B1.1 Reduction of ketones and aldehydes by hydrogen transfer All procedures were performed under argon atmosphere using previously degassed and distilled 2-propanol.

Example 17: Catalytic reduction of acetophenone in the presence of a ruthenium (II) complex The acetophenone reduction step catalyzed by complex (7) is described. The same method was used with complexes (6)-(9)-(10)-(11) and the results are shown in Table 1.

a) Reduction of the acetophenone catalyzed by complex (7) (7) (1.6 mg, 0.0021 mmol) by adding 5 ml of 2-propanol to bring the catalyst solution into 10 ml of Schlenk. Prepared. Agitation completely dissolved the complex over a period of several minutes. In a second Schlenk (50 ml), 240 μl of a pre-prepared solution containing the catalyst in 2-propanol and 0.4 ml of 0.1 M NaO ⁱ Pr solution was added under reflux to acetophenone (19 ml of 2-propanol) 240 μl, 2 mmol) solution. The start of the reaction was studied and when the complex was added. The molar ratio of acetophenone / catalyst / NaO ⁱ Pr was 20000/1/400 and the substrate concentration was 0.1M.

b) the procedure used for the reduced complex of acetophenone (7) catalyzed by complexes (6), (9), (10), (11), (7a), (8a) and (9a); A similar method was used to test the catalytic reduction of acetophenone using complexes (6), (9), (10), (11) (0.0021 mmol). The data is given in Table 1.

Example 18: Catalytic reduction of linear and cyclic dialkyl ketones, alkylaryl ketones, diaryl ketones and aldehydes in the presence of complex (7) 5 ml of complex (7) (1.6 mg, 0.0021 mmol) A catalyst solution was prepared in 10 ml Schlenk by adding 2-propanol. Agitation completely dissolved the complex over several minutes.

Separately, in a second Schlenk (50 ml), 240 μl of a pre-prepared solution containing the catalyst in 2-propanol and 0.4 ml of 0.1 M NaO ⁱ Pr solution was refluxed in 19 ml of 2-propanol. To a ketone or aldehyde solution (2 mmol). The start of the reaction was studied and when the complex was added. The molar ratio of substrate / catalyst / NaO ⁱ Pr was 20000/1/400 and the substrate concentration was 0.1M. Table 1 gives the GC analysis data.

Table 1. Catalytic reduction of ketones and aldehydes (0.1 M) to alcohols in the presence of complexes (6), (7), (9), (10), (11). The molar ratio of ketone / complex / NaO ⁱ Pr was equal to 20000/1/400. The reaction was carried out under reflux.
The molar ratio of ^[a] acetophenone / (7) / NaO ⁱ Pr was equal to 5000/1/100
^{[B] The} reaction was carried out at 60 ° C.
The molar ratio of ^[c] aldehyde / (7) / K ₂ CO ₃ was equal to 1000/1/500

Experimental results show that reduction of linear, cyclic and arylalkyl ketones and aldehydes to the corresponding alcohol in 2-propanol under reflux using complex (7) is very fast and is equivalent to 20000 substrate / catalyst The ratio indicates that it was completed within a few minutes (see text). The turnover frequency value (TOF) was between 200000 and 1800000 h ⁻¹ , depending on the steric and electronic properties of the substrate (Table 1). By examination of the literature data, the previously reported system except Matthew (Mathieu) complexes which exhibit TOF of 90000H ^-1, it indicates TOF for generally acetophenone less than 10000h ^-1 (H. Yang, M. Alvarez, N. Lugan, R. Mathieu, J. Chem. Soc., Chem. Commun. 1995, 1721), indicating that complex (7) is one of the most active hydrogen transfer catalysts. Furthermore, chloride derivatives (10) and (11) and alkoxide derivatives (9) with benzo [h] quinoline ligands containing Me or ^t Bu groups exhibit very high activity comparable to derivative (7). .

By way of example, the synthesis of key intermediates for the preparation of antihistamines and other pharmaceutical derivatives from benzhydryl, benzophenone is also provided. Furthermore, the reaction can be carried out starting from a well concentrated solution of acetophenone (1M) and removing the acetone produced by distillation.

Tests were performed for the catalytic reduction of acetophenone using complexes (8a), (9a) in a manner similar to the procedure used for complex (7a) and the data are given in Table 2.

Example 19: Catalytic reduction of linear and cyclic dialkyl ketones, alkyl aryl ketones and diaryl ketones in the presence of an osmium complex (7a) 5 ml of complex (7a) (1.8 mg, 0.0021 mmol) A catalyst solution was prepared in 10 ml Schlenk by adding 2-propanol. Agitation completely dissolves the complex over a period of several minutes.

Separately, in a second Schlenk (50 ml), 200 μl of a pre-prepared solution containing catalyst in 2-propanol and 0.4 ml of 0.1 M NaO ⁱ Pr solution was refluxed in 19 ml of 2-propanol. To a solution of ketone (2 mmol). The start of the reaction was studied and when the complex was added. The molar ratio of ketone / catalyst / NaO ⁱ Pr was 20000/1/400. Table 2 gives the GC analysis data.

Table 2. Catalytic reduction of ketone (0.1M) to alcohol in the presence of complexes (7a), (8a) and (9a). The molar ratio of ketone / complex / NaO ⁱ Pr was equal to 20000/1/400. The reaction was carried out under reflux.
^[A] The molar ratio of ketone / complex / NaOiPr was equal to 100,000 / 1/2000.

Example 20: Synthesis of benzhydryl 1.82 g of benzophenone (10 mmol) and 98 ml of 2-propanol were added to a 100 ml flask under an argon atmosphere and heated at reflux. 400 μl of a 0.1 M NaO ⁱ Pr solution in 2-propanol (2 ml) and a 2-propanol solution containing catalyst (7) (3 mg dissolved in 8 ml 2-propanol, 0.0039 mmol) was added. The molar ratio of benzophenone / catalyst / NaO ⁱ Pr was equal to 50000/1/1000. ¹ H NMR analysis of the mixture indicated that the reaction was complete after 2 hours. The solvent was evaporated to give a colorless residue extracted with 30 ml diethyl ether. The solution was then passed through a silica packed column to remove the catalyst and sodium alkoxide. The filtrate was treated with Na ₂ SO ₄ , filtered, and removal of the solvent yielded benzhydrol and dried under reduced pressure (10 ⁻² mmHg).

Isolated product: 1.6 g (87% yield).

B1.2 Reduction of ketones and imines by hydrogenation All procedures were performed under a hydrogen atmosphere using previously degassed and distilled methanol.

Example 21:
Reduction of linear and cyclic dialkyl ketones, alkylaryl ketones and imines catalyzed by hydrogenation in the presence of ruthenium complexes (7) and (9) and osmium complex (7a) complex (7) (1 The catalyst solution was prepared in 10 ml Schlenk by adding 2 ml methanol to .3 mg, 0.0017 mmol, or (9) 1.6 mg, 0.0017 mmol, or (7a) 1.5 mg, 0.0017 mmol) . Agitation completely dissolved the complex over a period of several minutes.

Separately, in a second Schlenk (25 ml), 0.5 ml of a pre-prepared solution containing 9.6 mg KO ^t Bu (0.086 mmol) and catalyst was added in pre-distilled methanol (7.6 ml). Added to a solution of ketone (4.3 mmol). The mixture was transferred to a temperature controlled reactor at 40 ° C. for ruthenium and 70 ° C. for osmium. Molecular hydrogen (H ₂ ) was introduced at a pressure of 5 bar. The start of the reaction was studied and when hydrogen was added. The molar ratio of ketone / catalyst / KO ^t Bu was 10000/1/200 and the substrate concentration was 0.5M. Table 3 gives the GC analysis data.

Table 3. Catalytic reduction of ketone (0.5M) to alcohol in the presence of complexes (7), (9) and (7a). The molar ratio of ketone / complex / KO ^t Bu was equal to 10,000 / 1/200. Temperature = 40 ° C. for ruthenium complexes (7) and (9) and 70 ° C. for osmium complex (7a). H ₂ pressure = 5 bar, solvent = methanol.
^[A] The molar ratio of ketone / complex / KO ^t Bu was equal to 5000/1/100
^[B] The molar ratio of ketone / complex / KO ^t Bu was equal to 50000/1/1000.
^{[C] From 1} H-NMR data, no reduction of olefinic bonds was observed.
The molar ratio of ^[d] imine / complex / KO ^t Bu was equal to 5000/1/100.

The use of these novel catalysts involves a high rate of ketone reduction with quantitative conversion to product within minutes. Therefore, these ruthenium complexes include many alcohols of the R ₂ CHOH type, and the R and R ′ groups are saturated or unsaturated linear or cyclic aliphatic groups, or substituted alkyl groups, oxygen-containing substituents, halogens Ideal for the synthesis of many racemic mixtures of RR'CHOH, an aromatic hydrocarbon group that may or may not have atoms or pyridine. By this route, imines can also be reduced to amines.

B2. Catalytic test with chiral catalyst
B2.2 Asymmetric reduction of ketones by hydrogen transfer All procedures were carried out under an argon atmosphere using previously distilled and degassed 2-propanol.

Example 22: Enantioselective reduction of acetophenone (0.1 M) in the presence of chiral ruthenium complex (12)-(13)-(14)-(15) catalyzed by complex (12) The procedure for the effected enantioselective acetophenone reduction is described. The same method as for complexes (13)-(14)-(15) is used and the results are given in Table 4.

a) Enantioselective reduction of acetophone to 1-phenylethanol catalyzed by complex (12).
A catalyst solution was prepared in 10 ml Schlenk by adding 5 ml 2-propanol to complex (12) (1.9 mg, 0.002 mmol). Agitation completely dissolved the complex over several minutes.

Separately, in a second Schlenk (50 ml), 0.4 ml of a 0.1 M NaO ⁱ Pr solution in 2-propanol and 240 μl of the pre-prepared solution containing the catalyst were refluxed in 19 ml of 2-propanol. To a solution of ketone (2 mmol). The start of the reaction was studied and when the complex was added. The molar ratio of ketone / catalyst / NaO ⁱ Pr was 20000/1/400 and the substrate concentration was 0.1M. Table 4 gives the GC analysis data.

b) In a manner analogous to that used for the enantioselective reduction complex of acetophenone to 1-phenylethanol catalyzed by complexes (13)-(14)-(15) (12), complex (13 )-(14)-(15) (0.002 mmol) was used to test for the catalytic reduction of acetophenone and the results are given in Table 4.

Table 4. Enantioselective reduction of the ketone (0.1 M) to the corresponding chiral alcohol at 60 ° C. in the presence of a ruthenium (12)-(13)-(14)-(15) chiral complex. The molar ratio of ketone / complex / NaO ⁱ Pr was equal to 20000/1/1400.

B2.2 Asymmetric reduction of ketones by hydrogenation All procedures were carried out under a hydrogen atmosphere using methanol and ethanol previously distilled and degassed.

Example 23: Hydrogenated Complex (13) Catalytic Reduction of Alkyl Aryl Ketone in the State 2 ml of a methanol: ethanol mixture in a 7: 3 ratio (by volume) The catalyst solution was prepared in 10 ml Schlenk by adding to .0017 mmol). Agitation completely dissolved the complex over several minutes.

Separately, in a second Schlenk (25 ml), 0.5 ml of a pre-prepared solution containing 9.6 mg KO ^t Bu (0.086 mmol) and catalyst was added to a methanol: ethanol mixture (7: 3 by volume; To a solution of ketone (4.3 mmol) in 7.6 ml). The mixture was transferred to a temperature controlled reactor at 40 ° C. Molecular hydrogen (H ₂ ) was introduced at a pressure of 5 bar. The start of the reaction was studied and when hydrogen was added. The molar ratio of ketone / catalyst / KO ^t Bu was 10000/1/200 and the substrate concentration was 0.5M. Table 5 gives the GC analysis data.

Table 5. Catalytic reduction of ketone (0.5M) to the corresponding chiral alcohol in the presence of complex (13). The molar ratio of ketone / complex / KO ^t Bu was equal to 10,000 / 1/200. Temperature = 40 ° C. H ₂ pressure = 5 bar, solvent = methanol: ethanol mixture (volume ratio 7: 3).

Claims (23)

Formula (I)

(Where:
R ₁ is an aliphatic group or an aromatic group;
R ₂ , R ₃ and R ₄ are the same or different from each other, and are a hydrogen atom, an aliphatic group or an aromatic group, a halogen atom, an alkoxo group, a nitro group or a cyano group)
A ligand derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group at the second position, represented by R ₁ is methyl and R ₂ , R ₃ and R ₄ are H, derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group in position 2 according to claim 1 Ligand. The benzo [h] quinoline having a —CHR ₁ —NH ₂ group at the second position according to claim 1, wherein R ₁ is tert-butyl and R ₂ , R ₃ and R ₄ are H. Originated ligand. Formula (II)

Wherein M, X, L and L ′ are as follows:
M Group VIII transition metal selected from iron, ruthenium and osmium;
X halogen, hydrogen, alkoxide (OR);
L A ligand selected from the group consisting of:
a) a monodentate phosphine of the general formula PR ¹ R ² R ^{3 wherein} R ¹ , R ² and R ³ are equal or different from each other and are aliphatic or aromatic;
b) Z is, x is a hydrocarbon chain which is optionally substituted with priority equal _{PR '2 (CH 2) x} PR''2 diphosphine in 2, 3 or 4, R' and R '' equal or different, and, an aliphatic group or an aromatic _{group, PR '2 -Z-PR'} '2 type bidentate phosphine;
c) an optically active diphosphine;
And when ligand L is selected from group b) or c), m is equal to 1, and when ligand L is selected from group a), m is equal to 2, and in this case , ligand L that is equal or different;
L ′ Formula (Ib)

Wherein R ₁ is H, an aliphatic group or an aromatic group, and R ₂ , R ₃ and R ₄ are the same or different, and a hydrogen atom, an aliphatic group and an aromatic group, a halogen atom, (Alkoxo group, nitro group, cyano group)
A tridentate cyclometalated ligand derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group at the _second position
A transition metal complex represented by The transition metal complex according to claim 4 , wherein M is selected from ruthenium or osmium. When M is ruthenium and m is equal to 2, they have the formula (V)

(Where
X is halogen, hydrogen, alkoxide (OR);
L is an equal or different monodentate phosphine selected from group a);
L ′ is a CNN type tridentate ligand of formula (Ib))
The transition metal complex according to claim 5 , represented by When M is ruthenium and m is equal to 1, they are of formula (VI)

(Where
X is halogen, hydrogen or alkoxide (OR);
L is a bidentate phosphine selected from b) group or c) an optically active diphosphine selected from group;
L ′ is a CNN type tridentate ligand of the formula (Ib))
The transition metal complex according to claim 5 , represented by When M is osmium and m is equal to 2, they are of formula (VII)

(Where
X is halogen, hydrogen, alkoxide (OR);
L is an equal or different monodentate phosphine selected from group a);
L ′ is a CNN type tridentate ligand of the formula (Ib))
The transition metal complex according to claim 5 , represented by When M is osmium and m is equal to 1, the complex has the formula (VIII)

(Where
X is halogen, hydrogen, alkoxide (OR);
L is a bidentate phosphine selected from b) group or c) an optically active diphosphine selected from group;
L ′ is a CNN type tridentate ligand of the formula (Ib))
The transition metal complex according to claim 5 , represented by The transition metal complex according to any one of claims 4 to 9 , wherein X is chlorine or bromine. If L is a) a phosphine group, it is PPh _3, the transition metal complex according to any one of claims 4-9. If L is the group b) phosphine, which is _{PPh 2 (CH 2) 4 PPh} 2, the transition metal complex according to any one of claims 4-9. If L is a diphosphine of group c), which is ^{(R, S) -JOSIPHOS, (} S, R) -JOSIPHOS *, (S, S) -SKEWPHOS, (S) -MeO-BIPHEP, claim 4 The transition metal complex according to any one of to 9 . The transition metal complex according to any one of claims 4 to 9 , wherein R ₁ , R ₂ , R ₃ and R ₄ of the ligand L ′ of the formula (Ib) are H. The transition metal complex according to any one of claims 4 to 9 , wherein R ₁ is methyl, and R ₂ , R ₃ , and R ₄ of the ligand L 'of the formula (Ib) are H. . The transition metal according to any one of claims 4 to 9 , wherein R ₁ is tert-butyl and R ₂ , R ₃ and R ₄ of the ligand L 'of formula (Ib) are H. Complex. When R ₁ is methyl or tert-butyl, it can be obtained from 2-bromobenzo [h] quinoline or 2-chlorobenzo [h] quinoline by production of the corresponding oxime and subsequent catalytic reduction thereof. A method for producing the ligand described in 1. Formula (I) with a transition metal precursor in the presence of phosphine and base

Wherein R ₁ is H, an aliphatic group or an aromatic group, and R ₂ , R ₃ and R ₄ are equal or different, and a hydrogen atom, aliphatic group or aromatic group, halogen atom, alkoxo Group, nitro group, cyano group)
The method for producing a transition metal complex according to claim 4, which can be obtained by a reaction of a ligand derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group at the second position represented by: The metal precursor for making the complex is a precursor comprising a monodentate phosphine of the formula MX ₂ P _n (M = Ru, Os; X = Cl, Br; P = PPh ₃ ; n = 3, 4), A method for producing the transition metal complex according to claim 18 . Formula (I) for preparing a transition metal complex selected from iron, ruthenium and osmium

Wherein R ₁ is H, an aliphatic group or an aromatic group, and R ₂ , R ₃ and R ₄ are equal or different, and a hydrogen atom, aliphatic group or aromatic group, halogen atom, alkoxo Group, nitro group, cyano group)
Use of a ligand derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group in the 2 position as shown by Use of the transition metal complex according to any one of claims 4 to 16 as a catalyst in a reduction reaction by hydrogen transfer or using hydrogen gas. Formula (I) for the same transition metal precursor in the presence of phosphine and base

Wherein R ₁ is H, an aliphatic group or an aromatic group, and R ₂ , R ₃ and R ₄ are equal or different, and a hydrogen atom, aliphatic group or aromatic group, halogen atom, alkoxo Group, nitro group, cyano group)
Can be obtained in situ upon catalytic reduction by reaction of a ligand derived from benzo [h] quinoline having a —CHR ₁ —NH ₂ group in position 2 as shown by Item 17. The transition metal complex according to any one of Items 4 to 16 . The metal precursor for producing the complex is a precursor comprising a monodentate phosphine of formula MX ₂ P _n (M = Ru, Os; X = Cl, Br; P = PPh ₃ ; n = 3, 4) transition metal complex according to claim 2 2.